Drug delivery device

ABSTRACT

A drug delivery device comprising;
         a housing;   a cylindrical member configured to be rotatably supported inside the housing, wherein the outer surface of the cylindrical member is provided with a track comprising a sequence of encoded images; and   a sensor directed at the track of the cylindrical member and configured to detect features of the encoded images.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a divisional application of U.S. patentapplication Ser. No. 14/232,502, filed Jan. 13, 2014 which is a 35U.S.C. 371 National Application of PCT/EP2012/063622 filed Jul. 12,2012, which claims priority to European Patent Application No.11174121.1 filed Jul. 15, 2011 and U.S. Provisional Patent ApplicationNo. 61/570,307, filed Dec. 14, 2011 the entire contents of which areincorporated entirely herein by reference.

FIELD

The present invention relates to a drug delivery device.

BACKGROUND

Pen type drug delivery devices have application where regular injectionby persons without formal medical training occurs. This is increasinglycommon among patients having diabetes where self-treatment enables suchpatients to conduct effective management of their diabetes.

For good or perfect glycemic control, the dose of insulin or insulinglargine has to be adjusted for each individual in accordance with ablood glucose level to be achieved. The present invention relates toinjectors, for example hand-held injectors, especially pen-typeinjectors, that is to injectors of the kind that provide foradministration by injection of medicinal products from a multidosecartridge. In particular, the present invention relates to suchinjectors where a user may set the dose.

A user undertaking self-administration of insulin will commonly need toadminister between 1 and 80 International Units.

SUMMARY

A first aspect of the invention provides a drug delivery devicecomprising;

-   -   a housing;    -   a cylindrical member configured to be rotatably supported inside        the housing, wherein the outer surface of the cylindrical member        is provided with a track comprising a sequence of encoded        images; and    -   a sensor directed at the track of the cylindrical member and        configured to detect features of the encoded images.

The track may be a helical track and the housing and the cylindricalmember may be configured such that the cylindrical member moves in afirst axial direction relative to the housing when rotated in a firstrotational direction relative to the housing.

The cylindrical member may be configured to be rotated from an initialposition into a number of discrete rotational positions, wherein eachsuccessive rotational position is represented by the next in thesequence of encoded images. The encoded images may be optically encodedimages and the sensor may be an optical sensor configured to detectlight intensity values at multiple locations on each encoded image. Thehousing may also support a light source configured to illuminate thetrack.

The encoded image may be an optically encoded image that is arepresentation of a value. The value could correspond to a position of acylindrical member. The cylindrical member could be operationallycoupled to a dose setting and/or dispensing mechanism. The position ofthe cylindrical member could correspond to a dialled dose size.

The sensor detecting the image may be connected to a processor thatdetermines the corresponding value. Having a certain value encoded intoan optical image could allow for absolute value determination.

The successive rotational position of the cylindrical member may berepresented by the next in the sequence of encoded images. The images inthe sequence may be separated, e.g. the images may be separated by awhite separation space. This may support identification of theindividual image.

An image could be as complex as a figurative landscape or portraitimage. Having images of, e.g., 81 different faces could be used torepresent 81 different values. Hence, each image has encoded a certainvalue.

An image, however, may be less complex, and represent a rather abstractpattern. Again, e.g., 81 different images could be used to represent 81different values. It is immediately understood that the number of valuesis almost arbitrary. The determination of a value corresponding to anencoded image is merely dependent upon the capabilities of the sensor.

The encoding may comprise light intensities. The light intensities couldcomprise black and white values, grey levels, or colors.

The light intensity could be an integral value of the area of the image.A sensor could determine the grey level of the entire area of imagewhich corresponds to a certain value that is encoded in the image. Forexample, a sensor capable of determining 256 different grey levels couldbe used to determine 256 absolute position values that are encoded in256 different images.

Alternatively, the light intensity could vary at multiple locationswithin the area of the image.

The light intensity variation at multiple locations could be encoded interms of patterns. A pattern could comprise the whole area of the image.A pattern could comprise a partial area of the image. The image areacould be segmented, e.g. into seven partial areas. Each partial areacould be either black or white. Together, the encoded image wouldrepresent a 7-bit code system. However, any number of segments orpartial areas may be used to make up an image that represents a codesystem with the respective number of bits.

The light intensity variation at multiple locations could be encoded interms of a matrix. The matrix could be a dot matrix.

The device may further comprise a processor configured to receiveelectrical signals from the sensor and to identify an encoded image fromthe received signals. The processor may be configured to interpret thesignals and to compare the interpreted signals to a stored record ofencoded images. Each encoded image may comprise a plurality of adjacentidentical code sections and the sensor may be configured to detectportions of two or more of the adjacent identical code sections.

The processor may be configured to receive image data from the sensorand to detect a geometric feature of the image data. The processor maybe configured to detect encoded information from a location of the imagethat is in a predefined position relative to the geometric feature. Theprocessor may be configured to detect encoded information from plurallocations of the image that are in different predefined positionsrelative to the geometric feature. Each predefined position relative tothe geometric feature may be defined by a pixel map comprising anarrangement of data bits.

The geometric feature may be a cross shaped feature of the image. Thecross shaped feature may separate four adjacent identical code sections.Each of the identical code sections may comprise an arrangement of databits. The processor may be configured to compare the received image datato the pixel map comprising an arrangement of data bits.

Each encoded image may be disposed within a boundary of a geometricfeature. The processor may be configured to compare the received imagedata to the pixel map comprising an arrangement of data bits and todetermine which of the pixels represents the centre of the predeterminedgeometric feature. The predetermined geometric feature may be a circularband.

Each data bit may be comprised of a plurality of pixels and each pixelof the pixel map may have an associated weighting value determined byits position within its respective data bit.

The device may further comprise a user actuatable plunger configured tocause expulsion of a drug from the drug delivery device and a switch,wherein depression of the plunger may be configured to cause the switchto switch from a first position to a second position. The device mayfurther comprise a display and the processor may control the operationof the display.

The processor may be configured to determine a discrete rotationalposition of the member using the reconstructed encoded image, todetermine a selected drug dose using the discrete rotational position ofthe member and to cause the selected drug dose to be displayed on thedisplay.

The outer surface of the cylindrical member may be further provided witha detectable surface texture. The sensor may be an optical sensor andmay be further configured to detect changes in light intensity values atthe location of the surface texture when the cylindrical member rotates.

The device may further comprise a lens disposed in a line of sight ofthe sensor.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments will now be described, by way of example only, withreference to the accompanying drawings, in which:

FIG. 1 shows a wireframe illustration of a drug delivery device suitablefor implementing the present invention;

FIG. 2 shows a schematic diagram of some of the electronic componentspresent in the drug delivery device of FIG. 1;

FIG. 3 shows a dose setting mechanism of a drug delivery device suitablefor use with the invention;

FIG. 4 shows detail of the dose setting mechanism of FIG. 3;

FIG. 5 shows a close up of the region marked ‘A’ in FIG. 3; and

FIG. 6 is an exploded view showing details of a driver forming part ofthe dose setting mechanism of FIGS. 3 to 5;

FIG. 7 shows an exemplary code section from an encoded member accordingto an embodiment of the invention;

FIG. 8 shows a template for creating an encoded image according to anembodiment of the invention;

FIG. 9a shows a typical field of view of an image sensor relative to across feature;

FIG. 9b shows a rearrangement of the image of FIG. 9 a;

FIG. 10 shows the position of pixels and data bits in a pixel map;

FIG. 11 is a table illustrating an encoding method which maximizes thenumber of white bits in an encoded image;

FIG. 12 shows 81 encoded images produced according to the table of FIG.11;

FIG. 13 shows a template for an encoded image;

FIG. 14 shows some alternative encoded image templates;

FIG. 15 shows a result of an image capture of the template of FIG. 13;

FIGS. 16a-f illustrate a basic example of a circle detection algorithm;

FIG. 17 shows the position of pixels in a pixel map;

FIG. 18 shows 81 encoded images produced with the template of FIG. 13.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Referring firstly to FIG. 1, a wireframe illustration of a portion of adrug delivery device 100 according to embodiments of the invention isshown. The device 100 shown in FIG. 1 is a pen type injection device,having an elongate cylindrical shape, for setting and delivering amedicament, such as insulin. The device 100 comprises a housing 102having a first housing part 104 and a second housing part 106, only aportion of which can be seen at the far left side of FIG. 1. A rotatabledial 108 is located at a first (or proximal) end of the first housingpart 104. The rotatable dial 108 has substantially the same outerdiameter as the first housing part 104. The second housing part 106 maybe detachably connected to the second end of the first housing part 104.The second housing part 106 is configured to have a needle (not shown)or similar drug delivery apparatus attached to it. To achieve this, thesecond (or distal) end of the second housing part 106 may have athreaded portion. The threaded portion may have a smaller diameter thanthe remainder of the second housing part 106

A sensor 112 is supported on the first housing part 104. The sensor 112may be received in a recess or window in the first housing part 104. Thesensor 112 may comprise an add-on module, as shown. In some otherembodiments, the sensor 112 may be integral with the housing 102. Insome embodiments, the sensor 112 is an optical sensor. Optical sensorsof the type manufactured by Avago Technologies may be suitable for usein the present invention. The first housing part 104 may also support adisplay (not shown in FIG. 1 but shown as 210 in FIG. 2). The display210 may be an LCD display, a segmented display or any other suitabletype of display. The display 210 may be located above the sensor 112. Anumber of electronic components, described in greater detail withreference to FIG. 2, may be supported in the recess or window.

An encoded member 406 is rotatably mounted inside the first housing part104. The encoded member 406 is preferably a hollow cylinder andcomprises, on its outer surface, a helical track 110. This helical track110 comprises encoded information which is detectable by the sensor 112.The encoded member may be coupled to and configured to rotate with therotatable dial 108.

The first housing part 104 contains a drug dose setting and deliverymechanism (not shown). The second housing part 106 contains a drugcartridge (not shown). The drug contained in the drug cartridge may be amedicament of any kind and may preferably be in a liquid form. The drugdelivery mechanism of the first housing part 104 may be configured toengage with the drug cartridge of the second housing part 106 tofacilitate expulsion of the drug. The second housing part 106 may bedetached from the first housing part 104 in order to insert a drugcartridge or to remove a used cartridge. The first and second housingparts 104, 106 may be connected together in any suitable way, forexample with a screw or bayonet type connection. The first and secondhousing parts 104, 106 may be non-reversibly connected together in sucha way as the drug cartridge is permanently contained with the drugdelivery device 100. Further the first and second housing parts 104, 106may form part of a single housing part.

The rotatable dial 108 is configured to be rotated by hand by a user ofthe drug delivery device 100 in order to set a drug dose to bedelivered. This process is known as “dialling” a dose. The dial 108 maybe connected to an internal threading system which causes the dial 108to be displaced axially from the housing 102 as it is rotated in a firstdirection. The dial 108 may be rotatable in both directions or only in afirst direction. The device 100 is configured, once a drug dose has beenset by rotation of the rotatable dial 108, to deliver the set drug dosewhen a user exerts an axial force at the proximal end of the device. Therotatable dial 108 may support a button (not shown) which must bedepressed in order to deliver the set drug dose. The display 210 may beconfigured to display information on the drug dose which has been setand/or delivered. The display 210 may further show additionalinformation, such as the actual time, the time of the lastusage/injection, a remaining battery capacity, one or more warningsigns, and/or the like.

Referring now to FIG. 2, a schematic diagram of electrical circuitry 200forming part of the drug delivery device 100 is shown. The circuitry 200comprises a microprocessor 202, a non-volatile memory such as a ROM 204,a volatile memory such as a RAM 206, a display 210, the sensor 112, oneor more LEDs 212, a switch 216 and a bus 208 connecting each of thesecomponents. The circuitry 200 also comprises batteries 214 or some othersuitable source of power for providing power to each of the components.It will be apparent to the skilled person that other light sources, toreplace the LED 212, may be suitable, for example incandescent bulbsetc.

The ROM 204 may be configured to store software and/or firmware. Thissoftware/firmware may control operations of the microprocessor 202. Themicroprocessor 202 utilises RAM 206 to execute the software/firmwarestored in the ROM to control operation of the display 210. As such themicroprocessor 202 may also comprise a display driver.

The microprocessor 202 is configured to receive signals from the sensor112 and is configured to interpret these signals. Information isprovided on the display 210 at suitable times by operation of thesoftware/firmware and the microprocessor 202. This information mayinclude measurements determined from the signals received by themicroprocessor 202 from the sensor 112. For example, the sensor 112 maybe an optical sensor configured to capture pixelated greyscale images ofthe encoded information. The captured image data is then sent to themicroprocessor 202.

The one or more LEDs 212 are directed at the encoded member 406 in orderto illuminate the encoded information of the helical track 110. Thisallows the sensor 112 to detect the encoded information. For example,the sensor 112 may detect the intensity pattern of light reflected fromthe helical track 110. The LED 212 and sensor 112 may be configured tooperate at various wavelengths of light. The LED 212 and sensor 112 may,for example, operate in infra-red. The LED 212 and sensor 112 may be anintegrated unit or may comprise separate units.

A fuller explanation of the operation of the dose setting and deliverymechanism supported within the second housing part 106 will now be givenwith reference to FIGS. 3 to 6. FIG. 3 is a cross-sectional view of adose setting mechanism 400 of a drug delivery device. FIG. 4 is adetailed view of a portion of the dose setting mechanism 400. FIG. 5illustrates a close up view of the region marked ‘A’ in FIG. 3.

The dose setting mechanism 400 comprises an outer housing 404, an innerhousing 408 and the encoded member 406. These components are preferablyhollow cylinders arranged concentrically. The encoded member 406 isdisposed between the outer and inner housings. The inner housing 408comprises a groove 432 provided along an external surface 434 of theinner housing 408. A groove guide 436 provided on an inner surface 438of the encoded member 406 is rotatably engaged with this groove 432. Theencoded member 406 has information encoded on its outer surface 440 aswill be described in more detail below with reference to FIG. 7.

A dose dial grip 402 is located at a proximal end of the outer housing404. The dose dial grip 402 is disposed about an outer surface of aproximal end of the encoded member 406. An outer diameter of the dosedial grip 402 preferably corresponds to the outer diameter of the outerhousing 404. The dose dial grip 402 is secured to the encoded member 406to prevent relative movement between these two components. The dose dialgrip 402 is represented in the external view of FIG. 1 by the rotatabledial 108. The dose dial grip 402 supports a dose button 416 which has asprung bias in a proximal direction and is configured to be depressedinto the dose dial grip 402 by a user of the device 100.

A spindle 414 is disposed centrally within the mechanism 400. Thespindle 414 is provisioned with at least one helical groove. In theembodiment depicted, the spindle 414 has two opposite handed overlappinggroove forms that preferably extend over at least a majority of a lengthof the spindle. Each groove form is effectively continuous over a numberof turns. In one preferred arrangement, each groove of the spindle 414engages either a non-continuous helical groove form on a body portion oron a driver. Preferably, either or both a non-continuous thread form ona body and a driver consists of less than one complete turn of thread. Afirst thread of the spindle 414 is configured to connect with a portionof the inner housing 408.

The dose setting mechanism 400 also comprises a spring 401, a clutch 405and a driver 409 having a first driver portion 407 and a second driverportion 412. These driver portions 407, 412 extend about the spindle414. Both the first and the second driver portions 407, 412 aregenerally cylindrical. The clutch 405 is disposed about the driver 409.In one arrangement, the first driver portion 407 comprises a firstcomponent part 410 and a second component part 411. Alternatively, thefirst driver portion 407 is an integral component part.

With the dose setting mechanism 400, as a user dials a dose with thedose dial grip 402, the metal spring 401 is selected to be strong enoughto maintain engagement of both clutched couplings: the clutched couplingbetween the clutch 405 and the encoded member 406 and clutched couplingbetween the first driver portion 407 and second driver portion 412. Theencoded member 406 is coupled to the dose dial grip 402 such that when auser rotates the dose dial grip 402, the encoded member 406 alsorotates. As the encoded member 406 is rotated in a first rotationaldirection, it moves axially in a proximal direction due to its threadedconnection to the inner housing 408.

When the drug delivery device is being dispensed, the user applies anaxial load to the dose button 416 located at the proximal end of themechanism 400. The dose button 416 is axially coupled to the clutch 405and this prevents relative axial movement. Therefore, the clutch 405moves axially towards the cartridge end or the distal end of the dosesetting mechanism 400. This movement disengages the clutch 405 from theencoded member 406, allowing for relative rotation while closing up theGap ‘a’. The clutch 405 is prevented from rotating relative to a clicker420 and hence relative to the inner housing 408. However, in thisscenario, the coupling between the first driver portion 407 and thesecond driver portion 412 is also prevented from becoming disengaged.Therefore, any axial load on the spindle 414 only disengages the firstand second driver portions 407, 412 when the dose button 416 is notaxially loaded. This therefore does not happen during dispense.

A dose limiter 418 (visible in FIG. 4) is provided on first driverportion 407 and in the illustrated arrangement comprises a nut. The doselimiter 418 has an internal helical groove matching the helical grooveof the first driver portion 407. In one preferred arrangement, the outersurface of the dose limiter 418 and an internal surface of the innerhousing 408 are keyed together by way of splines. This prevents relativerotation between the dose limiter 418 and the housing 408 while allowingrelative longitudinal movement between these two components.

FIG. 6 shows in detail a first arrangement of the first driver portion407 and the second driver portion 412 illustrated in FIGS. 3 to 5. Asillustrated in FIG. 10, the second driver portion 412 is generallytubular in shape and comprises at least one drive dog 450 located at adistal end of the second driver portion 412. The first driver portion407 also has a generally tubular shape and comprises a plurality ofrecesses 452 sized to engage with the drive dog 450 on the second driverportion 412. The construction of the drive dog and recesses allowdisengagement with the drive dog 450 when the first and second driverportions are axially pushed together. This construction also creates arotational coupling when these components are sprung apart.

In some embodiments, the first driver portion 407 comprises a firstportion (first component part) 410 that is permanently clipped to asecond portion (second component part) 411. In this arrangement, thesecond component part 411 comprises the plurality of recesses 452 andthe first component part 410 includes the outer groove for the doselimiter 418 nut as well as an internal groove 454. This internal groove454 is used to connect to the spindle 414 and drives the spindle 414during dose administration. In the illustrated embodiment, the internalgroove 454 comprises a part helical groove rather than a completehelical groove. One advantage of this arrangement is that it isgenerally easier to manufacture.

One advantage of this dose setting mechanism 400 utilizing the innerhousing 408 is that the inner housing 408 can be made from anengineering plastic that minimizes friction relative to the encodedmember 406 groove guide 436 and the groove 432. For example, one such anengineering plastic could comprise Acetal. However, those skilled in theart will recognize that other comparable engineering plastics having alow coefficient of friction could also be used. Using such anengineering plastic enables the material for the outer housing 404 to bechosen for aesthetic or tactile reasons with no friction relatedrequirements since the outer housing 404 does not engage any movingcomponents during normal operation.

The groove guide 436 on the inner surface 438 of the member 406 mayextend over a single turn or over a partial turn. Alternatively, thisgroove guide 436 may comprise several turns. The member 406 may be madeof a plastic material. The inclusion of an inner housing 408 enables theencoded member 406 to have a helical thread or groove guide 436 on theinner surface 438 rather then the outer surface 440. This results in anumber of advantages. For example, this results in the advantage ofproviding more surface area along the outer surface 440 of the encodedmember 406 for the helical track 110. Another advantage is that thisinner groove 436 is now protected from dirt ingress. In other words, itis more difficult for dirt to become logged in this inner grooveinterface than if the groove were provided along the outer surface 440of the encoded member 406. This feature is particularly important for are-useable drug delivery device which is required to function over amuch longer period of time compared to a non re-useable device.

The effective driving diameter (represented by ‘D’) of the groovedinterface between the encoded member 406 and the inner housing 408 isreduced compared to certain known drug delivery devices for the sameouter body diameter. This improves efficiency and enables the drugdelivery device to function with a lower pitch (represented by ‘P’) forthis groove and groove guide connection. In other words, as the helixangle of the thread determines whether when pushed axially, the encodedmember will rotate or lock to the inner body wherein this helix angle isproportional to the ratio of P/D.

A window 442 in the outer housing 404 of the drug delivery device 100can be seen in FIG. 3. This window 442 may be configured to receive aninsert (not shown), comprising the microprocessor 202, ROM 204, RAM 206,display electronics, sensor 112, LED 212, switch 216 and batteries 214previously described. The sensor and LED 212 may be supported on alowermost surface of the insert, so as to have direct access to theencoded member 406. The display 210 (not shown) may be disposed on topof the insert or may be integral with the insert. The display 210 may belarger than the window 442 and may therefore protrude from the outerhousing 404. Alternatively, the display 210 may be configured to bereceived by the window 442 such that the display 210 is flush with theouter surface of the outer housing 404.

The dose setting mechanism 400 illustrated in FIG. 3-6 is configured tobe re-set to an initial position after the medicament in the attacheddrug cartridge has been expelled. This allows a new cartridge to beinserted and the drug delivery device 100 to be re-used. This re-settingmay be achieved by pushing axially on the distal end of the spindle 414i.e. the end which usually engages with the drug cartridge and does notrequire any mechanism associated with removal of a cartridge holder. Asillustrated in FIGS. 3 and 4, when the first driver portion 407 ispushed axially towards the second driver portion 412 (i.e., pushed in aproximal direction) the driver 409 is de-coupled from the rest of thedose setting mechanism 400.

An axial force on the spindle 414 causes the spindle 414 to rotate dueto its threaded connection to the inner housing 408. This rotation andaxial movement of the spindle 414 in turn causes the first driverportion 407 to move axially towards the second driver portion 412. Thiswill eventually de-couple the first driver portion 407 and second driverportion 412.

This axial movement of the first driver portion 407 towards the seconddriver portion 412 results in certain advantages. For example, oneadvantage is that the metal spring 401 will compress and will thereforeclose the Gap ‘a’ illustrated in FIGS. 3-5. This in turn prevents theclutch 405 from disengaging from the clicker 420 or from the encodedmember 406. The second driver portion 412 is prevented from rotationsince it is splined to the clutch 405. The clicker 420 is splined to theinner housing 408. Therefore, when the Gap ‘a’ is reduced or closed up,the second driver portion 412 cannot rotate relative to either the innerhousing 408 or the encoded member 406. As a consequence, the encodedmember 406 cannot rotate relative to the inner housing 404. If theencoded member 406 is prevented from rotating then, as the spindle 414is retracted back into the dose setting mechanism 400 and therebyre-set, there will be no risk of the encoded member 406 being pushed outof the proximal side of the dose setting mechanism 400 as a result of aforce being applied on the spindle 414.

Another advantage of a dose setting mechanism 400 comprising an innerhousing 408 is that the dose setting mechanism 400 can be designed, witha slight modification, as a drug delivery device platform that is nowcapable of supporting both re-settable and non-resettable drug deliverydevices. As just one example, to modify the re-settable dose settingmechanism 400 variant illustrated in FIGS. 3-6 into a non-resettabledrug delivery device, the first component part 410 and the secondcomponent part 411 of the first driver portion 407 and the second driverportion 412 can be moulded as one unitary part. This reduces the totalnumber of drug delivery device components by two. Otherwise, the drugdelivery device illustrated in FIGS. 3-6 could remain unchanged. In sucha disposable device, the second housing part 106 would be fixed to thefirst housing part 104 or alternatively made as a single one piece bodyand cartridge holder.

The dose setting mechanism described above is merely one example of amechanism suitable for supporting the encoded member 406 and forimplementing the present invention. It will be apparent to the skilledperson that other mechanisms may also be suitable. For example, amechanism which does not include an inner housing 408, but in which theencoded member 406 is still visible to the sensor 112 would be equallysuitable.

The outer surface 440 of the encoded member 406 comprises a helicaltrack 110, which is visible only in FIG. 1. This track 110 comprises aseries of encoded images, which may be equally spaced and equally sized.Each of these images may be a matrix of points within a grid or a barcode. The code may be printed, marked, indented, etched or similar ontothe helical track 110. The sensor 112 is configured to capture theseimages and to relay signals to the microprocessor 202. Themicroprocessor 202 is configured to employ software stored in the ROM204 to determine the content of each image, for example the positions ofthe matrix which have dots, and to identify a corresponding rotationalposition of the encoded member 406 relative to the sensor 112. Themicroprocessor 202 may achieve this by consulting a table stored in theROM 204 which relates the content of each image to a rotational positionof the encoded member 406 and hence to a drug dose which has beendialled or delivered. This result may be stored to the ROM 204 of thedevice 100 and/or displayed on the display 210.

The pitch of the helical track 100 is the same as the pitch of thegroove guide 436 of the encoded member 406 which engages with the innerhousing groove 432. Therefore, when the encoded member 406 rotates andmoves axially within the housing 102, the helical track 100 is alwayspositioned underneath the sensor 112.

A typical field of view for an optical sensor 112 suitable for use inthe present invention is 1 mm². Alignment of the encoded images of thetrack 110 with such a field of view can be difficult. In someembodiments, a lens (not shown) may be incorporated into the sensor 112to increase the field of view without an unacceptable deterioration insensitivity. This may ensure that each encoded image relating to adiscrete rotational position of the encoded member 406 is legible.

In some embodiments, each of the encoded images comprises a repeatedcode pattern. An exemplary encoded image 300 representing a singlerotational position is shown in FIG. 7. The encoded image 300 has anumber of identical code patterns 302. In this instance fourpoint-matrix code patterns 302 are arranged into a larger grid. Thesquare 304 represents the field of view of the sensor 112. The repeatedcode patterns 302 mean that sensor position does not need to be asaccurate as when only a single code pattern 302 is used. This allows forpositional variability of the sensor 112 due to tolerance build up.Tolerance may be more likely to build up in one direction than another.For example, it may be found that the vertical alignment of the sensor112 with the track 110 remains accurate but that variability in thecircumferential alignment is seen. In this case only two repeated codepatterns 302 may be used, arranged adjacent to one another along thelength of the track 110.

The microprocessor 202 is programmed to recognise the edges of each ofthe code patterns 302 and to determine the full code based upon partialviews of two or more identical code patterns 302. For example, where theencoded image 300 is a point-matrix code as shown in FIG. 7, and thesensor 112 is an optical sensor, the data output by the sensor 112 maycomprise an array of light intensity values. The microprocessor 202 mayuse these light intensity values to identify the rows and columns of thematrix. The microprocessor 202 also determines whether each point in thematrix is black or white. The microprocessor 202 may then compare thedata with a stored table relating the matrix pattern to a rotationalposition of the member 406. Where the encoded image 300 consists of aplurality of identical code patterns 302, the microprocessor 202 mayidentify the edges of each code pattern 302 in any known way. Themicroprocessor 202 may also then identify the rows and columns of anypartial view of the code patterns 302 and may use this identification tovirtually reconstruct one complete code pattern.

Where the device 100 is an insulin pen, a user of the device 100 maycommonly need to administer between 1 and 80 International Units ofinsulin. Therefore, the helical track 110 preferably has at least 81(including a zero position) discrete rotational positions, eachrepresented by a unique encoded image 300. Where the encoded images arepoint-matrices, each of the 81 encoded images may be substantiallydifferent, i.e. there may be several differences between any twomatrices. This allows for mistakes to be made by the microprocessor 202in identifying the layout of the matrix while still allowing themicroprocessor 202 to identify which rotational position the matrixencodes.

Further embodiments of encoded images suitable for use in the presentinvention will now be described with reference to FIGS. 8 to 12. FIG. 8shows a template 400 for creating an encoded image consisting of fouridentical pixel maps 402 arranged into a larger grid. Each pixel map 402may be comprised of a 22×22 pixel array. Each pixel map 402 comprisesseven information bits (numbered 1 to 7) and one parity bit. When anencoded image 300 is created, each of the bits may be filled in black orleft white.

The square 304 represents the field of view of the sensor 112. Thesensor 112 captures an image of the portion of an encoded image whichappears within its field of view. The field of view of the sensor 112 islarger than the repeated pixel maps 402 and so captures differentportions of each of the pixel maps 402. The image captured by the sensor112 is then analysed by the microprocessor 202 in order to reconstruct asingle pixel map 402 from the portions of each of the pixel maps 402present in the image. The position of the pixel maps 402 relative to thefield of view of the sensor 112 is determined by detection of a datumfeature. A datum feature is a geometric feature or shape which isdistinct from any features of the pixel maps 402. Once the position ofthe pattern within the field of view is determined, the true encodedpattern can be virtually generated by manipulation of the pixel datafrom the captured image.

In the embodiment shown in FIGS. 8 to 12 the geometric feature (or datumfeature) is a black cross 404 consisting of a horizontal band 406 and avertical band 408, surrounded by a white border. The term “cross” asused herein may refer to a shape comprising two straight arms whichintersect, preferably at right angles. Preferably the intersectionoccurs at a mid point of each of the two arms. The length and width ofthe bands 406, 408 is distinctly different from any pattern produced bypossible combinations of black and white bits within the pixel maps 402.

The sensor 112 captures a pixelated image in grayscale, with highintensity pixels representing white areas and low intensity pixelsrepresenting black areas of the pattern. The microprocessor 202 isconfigured to implement an algorithm to detect the cross feature withinthe image. The algorithm detects the strongest horizontal and verticallines, of a predetermined width, within the captured image. A line isassumed to be a band (horizontal or vertical) of low intensity pixels,surrounded by high intensity pixels. In order to accurately perform thisdetection, the arms of the cross and the pixels of the sensor 112 shouldhave substantially the same orientation. In other words, a nominal‘horizontal’ arm of the cross should preferably have the sameorientation as a row of pixels, however the alignment does not need tobe exact for the detection to be successful.

The cross detection algorithm for the horizontal band 406 may bedescribed mathematically as follows, where ‘n’ refers to a pixel rownumber.

-   -   Calculate the sum of the intensity values for the pixels within        each row:        ΣRow_(n=)Pixel_(n,1)+Pixel_(n,2)+Pixel_(n,3)+Pixel_(n,4) . . . .    -   Calculate the sum of row intensities over a range of rows. The        size of the range should match the pixel width of the horizontal        band 406 of the cross 404. In this example a 3 pixel band is        used:        Band_Sum_Row_(n)=ΣRow_(n−1)+ΣRow_(n)+ΣRow_(n+1)    -   Calculate the compound intensity gradient of the band        intensities.        Compound_Gradient_Row_(n)=(Band_Sum_Row_(n)−Band_Sum_Row_(n−1))+(Band_Sum_Row_(n)−Band_Sum_Row_(n+1))

Any row with a positive compound gradient indicates a light bandcompared to its surroundings. Any row with a negative compound gradientindicates a dark band compared to its surroundings. The greater themagnitude of the compound gradient, the higher the intensity changebetween the band and its surrounding. Therefore the strongest horizontalblack band within the image is identified by the highest magnitudenegative compound gradient. Thresholds can be included to ensure thatthe strongest band is of sufficient intensity, and that it is a distinctsolution from the next strongest band.

The same algorithm is then applied to the columns of the image to detectthe strongest vertical black band. By initially combining the intensityof each pixel into a summation of the intensity for each row and column,the number of calculations required to solve the algorithm issignificantly reduced when compared to continuing to consider, andconduct calculations on, each pixel individually. This results in areduction in power consumption of the microprocessor 202 as well as anincrease in the speed with which a determination of the rotationalposition of the encoded member 406 can be made.

Once the position of the cross 404 within the image is determined, thecaptured image can be manipulated to shift the cross feature into acorner, thereby recreating the fully encoded pattern within a singlequadrant of the manipulated image. FIG. 9a shows a typical field of viewof the sensor 112 relative to the cross 404. The portions of each pixelmap 402 captured by the sensor are labeled as zones 1 to 4. FIG. 9bshows a virtual rearrangement of the image of FIG. 9a to place the cross404 in one corner of the image and to reconstruct a full pixel map 402in one quadrant.

In reality some overlapping of each of the zones will occur, dependanton the actual image sensor 112 used, the size of the field of view andthe size of the encoded pattern. As the size of the encoded image 300and field of view of the sensor 112 are well controlled, themicroprocessor 202 is able to crop the image zones when rearranging theimage.

Once the manipulated image is obtained, the pixel data can beinterrogated to determine the encoded data. Use of the pixel maps 402ensures that each pixel within the manipulated image is assigned to aparticular data bit, dependant on its relative position to the cross404. The pixel map 402 can also assign a weighting value to each pixel.Weighting values are used to apply increased significance to pixelscontained within the body of a particular data bit than pixels at a databit boundary. Due to the pixelation of the captured image there is agreater degree of confidence in the colour (black or white) of thosepixels which are surrounded by other pixels within the same data bitthan those which are adjacent another data bit.

FIG. 10 shows the position of each pixel and data bit in a pixel map402. The position of each of the pixels comprising the data bits isrepresented by a number which is also the weighting value of that pixel.The weighted average intensity of each data bit can therefore bedetermined by the microprocessor 202. These weighted averages can becompared against threshold values to determine whether each data bit isblack or white. Threshold values may be fixed, or may be based onintensity values of the captured image to automatically compensate forvariations in image intensity. In this embodiment, a single parity bitis included to provide error checking. Alternatively, more data bitscould be assigned to error checking to increase the robustness of thedecoded data.

As previously mentioned, the device 100 may be able to deliver up to 80doses, such that there are 81 positions, including a zero position, ofthe encoded member 406 relative to the housing 102. This number ofpositions can be encoded within 7 bits of data. As 7 bits could be usedto encode up to 128 positions, a reduced coded set may be utilised,which maximises the number of white data bits.

The coded pattern shown in FIGS. 11 and 12 has a maximum of 4 black databits across the 7 data bits and parity bit. Therefore at least 50% ofthe data bits are always white, maximising the image contrast betweenthe cross 404 and the encoded data. This reduces the chance of an errorin the detection of the position of the cross 404 within the capturedimage. FIG. 11 is a table illustrating the sense (high or low) of eachbit for each of the 81 encoded positions for a “maximum white” code.FIG. 12 is a grid showing all 81 “maximum white” encoded images as theywould be printed on to the track 110 of the encoded member 406.

Referring now to FIGS. 13 to 18, further embodiments of encoded imagessuitable for use in the present invention are shown. FIG. 13 shows atemplate 500 for an encoded image. The template 500 has a circular blackband 502 as the geometric datum feature. The encoded data is containedwithin this circle 502, and consists of 7 binary data bits, numbered 1to 7. The internal area of the circle 502 is therefore split into 7segments and each segment is filled black to represent a “high” databit, or white to represent a “low” data bit.

The field of view of the sensor 112 encompasses the whole of the encodedimage and is arranged so as to capture an image containing the entireencoded image, including the circle 502. The position of the circle 502within the captured image is determined by an algorithm, and hence thelocation of each of the data bits can be determined.

FIG. 14 shows some possible alternative encoded image templates 503,504, 505, 506 having a differently shaped outer boundary (datum feature)and/or differently shaped data segments. Any suitable geometric shape orfeature could be used for the outer boundary and data segments.

The sensor 112 captures a pixelated image in greyscale, with highintensity pixels representing white, and low intensity pixelsrepresenting black, areas of the pattern. FIG. 15 shows a result of thisimage capture. The captured image 507 comprises a pixelated circularfeature 508. The image sensor 112 may have a pixel array of 22×22pixels.

The microprocessor 202 then implements an algorithm to detect theposition of the pixelated circular feature 508 within the image 507. Thesize of the circle 502 relative to the captured image 507 is known, asthe pattern generation and image field of view are well controlled. Thealgorithm therefore searches the captured image 507 for a feature of aknown shape and size. The output of the circle detection algorithm is asingle pixel at the centre of the pixelated circle 508.

Prior to circle detection, an 3×3 edge detection spatial filter and athreshold filter are applied to the captured image, to generate a binaryimage with white pixels representing edges. The circle detectionalgorithm assumes that each detected edge pixel could be located on anypart of the circumference of the pixelated circle 508, and therefore thecentre of the circle could be offset from that edge pixel in anydirection by a distance equal to the radius of the (printed) circle 502.

A virtual circle, of the same radius as the circle 502, is thereforecreated around each edge pixel. The virtual circle passes through aspecific set of pixels in the detection array. Each time a virtualcircle passes though a pixel in the detection array, a value associatedwith that pixel is incremented by 1. These virtual circles are generatedfor each edge pixel within the threshold filtered image. This routinegenerates a circle detection array containing an array of numbers. Thearray position with the highest number has the most virtual circlescrossing it and therefore this array position corresponds to thecaptured image pixel which is the most likely solution for the centre ofthe pixelated circle 508.

The circle detection array extends beyond the field of view of thecaptured image, as an edge pixel at an edge or corner of the capturedimage would generate a virtual circle which extends up to 1 radiusbeyond the captured image. It is therefore possible to detect theposition of a pixelated circle 508 the centre of which is outside of thefield of view of the captured image.

A basic example of the circle detection algorithm is illustrated inFIGS. 16a-f , using a simplified image with only four edge pixels. FIG.16a shows the four detected edge pixels on a circle detection array. InFIG. 16b a first virtual circle is created around a first of the edgepixels. Each pixel of the circle detection array that this virtualcircle passes through has a value associated with it incremented (from 0to 1). This process is repeated in FIG. 16c for the second edge pixel,in FIG. 16d for the third edge pixel and in FIG. 16e for the fourth edgepixel. Once this process has been completed for all of the detected edgepixels, the microprocessor 202 searches the array to find the largestvalue associated with a pixel. In this instance, one pixel has a valueof 4 and is determined to be the most likely centre of the circle, asshown in FIG. 16 f.

Due to the pixelation of the encoded pattern and circle 502, it ispossible that the centre of the circle will occur at a pixel vertex,rather than within a single pixel. In order to address this a 2×2spatial filter is applied to the circle detection array to average thearray value across four pixels. The highest value within the averagedcircle detection array defines the most likely pixel vertex solution forthe centre of the pixelated circle 508.

Threshold values and error checking can be applied within the algorithmto verify the results. Exemplary verification checks include:

-   -   The single pixel solution lies within the averaged pixel        solution    -   The most likely solution is distinct from other possible        solutions i.e. highest value in array/second highest value in        array>confidence factor    -   A sufficient number of valid edge pixels exist for the most        likely solution i.e. highest value in array>threshold    -   The centre pixel is within the captured image, such that all        encoded data pixels are within the captured image

Once the circle detection algorithm has identified and verified a pixelrepresenting the centre of the pixelated circle 508, the captured imagedata can be interrogated to determine the status of each data bit.Referring to FIG. 17, a pixel map 600 assigns each pixel within thecaptured image to a particular data bit, dependant on its relativeposition to the central pixel. The pixel map can also assign a weightingvalue to each pixel. Weighting values are used to apply increasedsignificance to pixels contained within the body of a particular databit relative to those pixels at a data bit boundary. FIG. 17 shows apixel map 600 in which each pixel is represented by a number which alsoindicates the weighting value given to that pixel.

The weighted average intensity of each data bit can therefore bedetermined by the microprocessor 202. These weighted averages can becompared against threshold values to determine whether each data bit isblack or white. Threshold values may be fixed, or may be based onintensity values of the captured image to automatically compensate forvariations in image intensity.

As with the previous embodiments, the 81 possible dose positions can beencoded within 7 bits of data. As 7 bits could encode up to 128positions, a reduced coded set can be utilised. These reduced coded setscan assist in maintaining the distinction of the pixelated circle 508relative to the encoded data within the circle.

The coded pattern, shown in full in FIG. 18, has a maximum of 4 blackdata bits across the 7 data bits. Therefore at least 60% of the databits are always white, maximising the image contrast between thecircular feature 508 and the encoded data. Alternatively, a codedpattern may be used which maximizes the number of black data bits in theencoded image. Alternatively, a coded pattern could be used whichmaximizes either white or black and is a Gray code (in which only onebit changes sense between successive encoded images).

Once the status of each data bit is determined, and validated againstthreshold values, the rotational position of the encoded member 406 canbe determined by comparing the coded output against a lookup table.

As well as determining the rotational position of the member 406, themicroprocessor 202 may also determine whether the device 100 is in adialling mode i.e. drug dose setting mode, or a drug delivery mode. Theswitch 216 may be any suitable micro-switch and may be coupled to boththe microprocessor 202 and the dose button 416 supported by therotatable dial 108. The state of the switch 216 may be changed when thedose button 416 is depressed and the microprocessor 202 may detect thischange. An indication of the mode (dialling or delivery) of the device100 may be displayed on the display 210.

When dispensing a selected dose, if for any reason the user does notdispense the full dose, the display 210 may be configured to show thedose which is remaining to be dispensed.

In some embodiments, the sensor 112 may be further configured tocontinuously measure the movement of the member 406 and to outputrelative translation data to the microprocessor 202. The microprocessor202 is configured to determine a discrete number of units dialled and/ordelivered from the received relative translation data. This allowsincremental positional encoding of the member 406. To aid the sensor indistinguishing relative movement, the encoded member 406 may be providedwith a particular surface finish such as shot-blasting or etching aswell as a plurality of markings, such as printed dots. This relativetranslational detection may be provided in addition to the encodedimages previously described and may act as a secondary positional check.In some alternative embodiments, successive images from the sensor 112may be compared via a simple algorithm in order determine an offsetbetween the images and therefore a rotational movement of the encodedmember.

It will be appreciated that the above described embodiments are purelyillustrative and are not limiting on the scope of the invention. Othervariations and modifications will be apparent to persons skilled in theart upon reading the present application. For example, although thehelical track 110 has been described as being applied to a memberintegral with the rotatable dose dial 108, the helical track 110 mayinstead be applied to any existing component of the drug dose settingmechanism 400 which moves rotationally, axially or both relative to thesensor 112 and which is, or can be made, visible to the sensor 112.Moreover, the disclosure of the present application should be understoodto include any novel features or any novel combination of featureseither explicitly or implicitly disclosed herein or any generalizationthereof and during the prosecution of the present application or of anyapplication derived therefrom, new claims may be formulated to cover anysuch features and/or combination of such features.

The term “drug” or “medicament”, as used herein, means a pharmaceuticalformulation containing at least one pharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a protein, apolysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or afragment thereof, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exendin-3 or exendin-4 or an analogue or derivative ofexendin-3 or exendin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N—(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N—(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

des Pro36 Exendin-4(1-39),

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;

or an Exendin-4 derivative of the sequence

des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010),

H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,

des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,

H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(S1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2;

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exendin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Antibodies are globular plasma proteins (˜150 kDa) that are also knownas immunoglobulins which share a basic structure. As they have sugarchains added to amino acid residues, they are glycoproteins. The basicfunctional unit of each antibody is an immunoglobulin (Ig) monomer(containing only one Ig unit); secreted antibodies can also be dimericwith two Ig units as with IgA, tetrameric with four Ig units liketeleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

The Ig monomer is a “Y”-shaped molecule that consists of fourpolypeptide chains; two identical heavy chains and two identical lightchains connected by disulfide bonds between cysteine residues. Eachheavy chain is about 440 amino acids long; each light chain is about 220amino acids long. Heavy and light chains each contain intrachaindisulfide bonds which stabilize their folding. Each chain is composed ofstructural domains called Ig domains. These domains contain about 70-110amino acids and are classified into different categories (for example,variable or V, and constant or C) according to their size and function.They have a characteristic immunoglobulin fold in which two β sheetscreate a “sandwich” shape, held together by interactions betweenconserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chain denoted by α, δ, ε, γ,and μ. The type of heavy chain present defines the isotype of antibody;these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies,respectively.

Distinct heavy chains differ in size and composition; α and γ containapproximately 450 amino acids and δ approximately 500 amino acids, whilep and c have approximately 550 amino acids. Each heavy chain has tworegions, the constant region (C_(H)) and the variable region (V_(H)). Inone species, the constant region is essentially identical in allantibodies of the same isotype, but differs in antibodies of differentisotypes. Heavy chains γ, α and δ have a constant region composed ofthree tandem Ig domains, and a hinge region for added flexibility; heavychains μ and ε have a constant region composed of four immunoglobulindomains. The variable region of the heavy chain differs in antibodiesproduced by different B cells, but is the same for all antibodiesproduced by a single B cell or B cell clone. The variable region of eachheavy chain is approximately 110 amino acids long and is composed of asingle Ig domain.

In mammals, there are two types of immunoglobulin light chain denoted byλ and κ. A light chain has two successive domains: one constant domain(CL) and one variable domain (VL). The approximate length of a lightchain is 211 to 217 amino acids. Each antibody contains two light chainsthat are always identical; only one type of light chain, κ or λ, ispresent per antibody in mammals.

Although the general structure of all antibodies is very similar, theunique property of a given antibody is determined by the variable (V)regions, as detailed above. More specifically, variable loops, threeeach the light (VL) and three on the heavy (VH) chain, are responsiblefor binding to the antigen, i.e. for its antigen specificity. Theseloops are referred to as the Complementarity Determining Regions (CDRs).Because CDRs from both VH and VL domains contribute to theantigen-binding site, it is the combination of the heavy and the lightchains, and not either alone, that determines the final antigenspecificity.

An “antibody fragment” contains at least one antigen binding fragment asdefined above, and exhibits essentially the same function andspecificity as the complete antibody of which the fragment is derivedfrom. Limited proteolytic digestion with papain cleaves the Ig prototypeinto three fragments. Two identical amino terminal fragments, eachcontaining one entire L chain and about half an H chain, are the antigenbinding fragments (Fab). The third fragment, similar in size butcontaining the carboxyl terminal half of both heavy chains with theirinterchain disulfide bond, is the crystalizable fragment (Fc). The Fccontains carbohydrates, complement-binding, and FcR-binding sites.Limited pepsin digestion yields a single F(ab′)2 fragment containingboth Fab pieces and the hinge region, including the H—H interchaindisulfide bond. F(ab′)2 is divalent for antigen binding. The disulfidebond of F(ab′)2 may be cleaved in order to obtain Fab′. Moreover, thevariable regions of the heavy and light chains can be fused together toform a single chain variable fragment (scFv).

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

The invention claimed is:
 1. A drug delivery device comprising; ahousing; a cylindrical member configured to be rotatably supportedinside the housing, wherein an outer surface of the cylindrical memberis provided with a track comprising a sequence of encoded images,wherein the encoded images each encode a discrete rotational position ofthe cylindrical member, wherein each encoded image comprises anidentical predetermined geometric feature, and wherein the predeterminedgeometric feature is a cross shaped feature that separates four adjacentidentical code sections; a sensor directed at the track of thecylindrical member and configured to capture an image of one or more ofthe encoded images; and a processor configured to: receive image datacorresponding to the captured image from the sensor; detect, using thereceived image data, a position of the predetermined geometric featurein the captured image; based on the position of the predeterminedgeometric feature in the captured image, reconstruct a single codesection from partial views of two or more of the identical code sectionsin the captured image; and detect, using the received image data,encoded information at at least one position in the captured image thatis predefined relative to the position of the predetermined geometricfeature and offset from the position of the predetermined geometricfeature.
 2. A drug delivery device as claimed in claim 1, wherein theprocessor is configured to detect encoded information at plurallocations in the image that are in different predefined positionsrelative to the geometric feature.
 3. A drug delivery device as claimedin claim 2, wherein each predefined position relative to the geometricfeature is defined by a pixel map comprising an arrangement of databits.
 4. A drug delivery device as claimed in claim 1, wherein each ofthe identical code sections comprises an arrangement of data bits.
 5. Adrug delivery device as claimed in claim 1, wherein the processor isconfigured to compare the received image data to a pixel map comprisingan arrangement of data bits.
 6. A drug delivery device as claimed inclaim 3, wherein each data bit in the pixel map is comprised of aplurality of pixels and wherein each pixel of the pixel map has anassociated weighting value determined by its position within itsrespective data bit.
 7. A drug delivery device as claimed in claim 1,wherein the processor is configured: to determine a discrete rotationalposition of the cylindrical member using the received image data; todetermine a selected drug dose using the discrete rotational position ofthe member; and to cause the selected drug dose to be displayed on adisplay.
 8. A drug delivery device as claimed in claim 1, wherein theprocessor is configured: to determine a succession of discreterotational positions of the cylindrical member using the received imagedata; and to determine a direction of rotation of the cylindrical memberusing the succession of discrete rotational positions.
 9. A drugdelivery device comprising; a housing; a cylindrical member configuredto be rotatably supported inside the housing, wherein an outer surfaceof the cylindrical member is provided with a track comprising a sequenceof encoded images, wherein the encoded images each encode a discreterotational position of the cylindrical member, and wherein each encodedimage comprises an encoded pattern disposed within a boundary of anidentical predetermined geometric feature; a sensor directed at thetrack of the cylindrical member and configured to capture an image ofone or more of the encoded images, wherein a field of view of the sensoris controlled such that the identical predetermined geometric featurehas a known pixel size within the captured image; and a processorconfigured to: receive image data corresponding to the captured imagefrom the sensor; search the captured image for a pixelated featurehaving a shape of the predetermined geometric feature and the knownpixel size; detect, using the received image data, encoded informationat at least one position in the captured image that is predefinedrelative to the position of the predetermined geometric feature andoffset from the position of the predetermined geometric feature whereineach encoded image is disposed within a boundary of the geometricfeature.
 10. A drug delivery device as claimed in claim 9, wherein theprocessor is configured to compare the received image data to a pixelmap comprising an arrangement of data bits and to determine which pixelrepresents a center of the predetermined geometric feature.
 11. A drugdelivery device as claimed in claim 9, wherein the predeterminedgeometric feature is a circular band.